6WQ3

Crystal Structure of Nsp16-Nsp10 Heterodimer from SARS-CoV-2 in Complex with 7-methyl-GpppA and S-adenosyl-L-homocysteine.

6WQ3 の概要

• エントリーDOI: 10.2210/pdb6wq3/pdb
• 分子名称: 2'-O-methyltransferase, Non-structural protein 10, S-ADENOSYL-L-HOMOCYSTEINE, ... (8 entities in total)
• 機能のキーワード: structural genomics, center for structural genomics of infectious diseases, csgid, nsp16, nsp10, complex, 7-methyl-gpppa, s-adenosyl-l-homocysteine, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51232.10

構造登録者

Minasov, G.,Shuvalova, L.,Rosas-Lemus, M.,Brunzelle, J.S.,Kiryukhina, O.,Satchell, K.J.F.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2020-04-28, 公開日: 2020-05-06, 最終更新日: 2024-02-28)

主引用文献

Rosas-Lemus, M.,Minasov, G.,Shuvalova, L.,Inniss, N.L.,Kiryukhina, O.,Brunzelle, J.,Satchell, K.J.F.
High-resolution structures of the SARS-CoV-2 2'- O -methyltransferase reveal strategies for structure-based inhibitor design.
Sci.Signal., 13:-, 2020

PubMed Abstract: There are currently no antiviral therapies specific for SARS-CoV-2, the virus responsible for the global pandemic disease COVID-19. To facilitate structure-based drug design, we conducted an x-ray crystallographic study of the SARS-CoV-2 nsp16-nsp10 2'--methyltransferase complex, which methylates Cap-0 viral mRNAs to improve viral protein translation and to avoid host immune detection. We determined the structures for nsp16-nsp10 heterodimers bound to the methyl donor -adenosylmethionine (SAM), the reaction product -adenosylhomocysteine (SAH), or the SAH analog sinefungin (SFG). We also solved structures for nsp16-nsp10 in complex with the methylated Cap-0 analog mGpppA and either SAM or SAH. Comparative analyses between these structures and published structures for nsp16 from other betacoronaviruses revealed flexible loops in open and closed conformations at the mGpppA-binding pocket. Bound sulfates in several of the structures suggested the location of the ribonucleic acid backbone phosphates in the ribonucleotide-binding groove. Additional nucleotide-binding sites were found on the face of the protein opposite the active site. These various sites and the conserved dimer interface could be exploited for the development of antiviral inhibitors.

PubMed: 32994211
DOI: 10.1126/scisignal.abe1202

実験手法

X-RAY DIFFRACTION (2.1 Å)